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PubMed2003

Dissociable effects of dopaminergic therapy on spatial versus non-spatial working memory in Parkinson's disease.

There is now evidence for definite and early cognitive deficits in Parkinson's disease (PD), involving, in particular, executive functions and working memory. However, the distinction between visuo-spatial and non-spatial working memory deficits and the impact of dopamine on these deficits are still open to debate. The aim of this study was therefore to investigate cognitive and motor performance in PD patients in two conditional associative learning tasks requiring either spatial or non-spatial visual working memory. The subject had to point to visual targets according to the visual characteristics of memorised visual cues (colour, position and form). To assess the effect of L-dopa therapy, PD patients were studied over two consecutive days: one ON/OFF group of nine PD patients with treatment (ON condition) on the first day and without treatment (OFF condition) on the second day; and another OFF/ON group of nine PD patients tested on reverse. The PD groups were compared to a control group of nine age-matched healthy subjects. Our main data demonstrate that: (1) in PD patients with OFF treatment, the response time of manual pointing is increased mainly in the non-spatial working memory task; and (2) in PD patients with ON treatment, either the response time is normal (on the first day) or is increased in both visuo-spatial and non-spatial tasks. We suggest that this dissociation between spatial versus non-spatial working memory deficits in non-medicated PD might be related to compensatory mechanisms that occur following fronto-striatal dysfunction.

Adult↗
PubMed1999

Threshold relationship between lesion extent of the cholinergic basal forebrain in the rat and working memory impairment in the radial maze.

The cholinergic basal forebrain (CBF) degenerates in Alzheimer's Disease (AD), and the degree of this degeneration correlates with the degree of dementia. In the present study we have modeled this degeneration in the rat by injecting various doses of the highly selective immunotoxin 192 IgG-saporin (192-sap) into the ventricular system. The ability of 192-sap-treated rats to perform in a previously learned radial maze working memory task was then tested. We report here that 192-sap created lesions of the CBF and, to a lesser extent, cerebellar Purkinje cells in a dose-dependent fashion. Furthermore, we found that rats harboring lesions of the entire CBF greater than 75% had impaired spatial working memory in the radial maze. Correlational analysis of working memory impairment and lesion extent of the component parts of the CBF revealed that high-grade lesions of the hippocampal-projecting neurons of the CBF were not sufficient to impair working memory. Only rats with high-grade lesions of the hippocampal and cortical projecting neurons of the CBF had impaired working memory. These data are consistent with other 192-sap reports that found behavioral deficits only with high-grade CBF lesions and indicate that the relationship between CBF lesion extent and working memory impairment is a threshold relationship in which a high degree of neuronal loss can be tolerated without detectable consequences. Additionally, the data suggest that the CBF modulates spatial working memory via its connections to both the hippocampus and cortex.

Animals↗
PubMed1997

Differential activation of the caudate nucleus in primates performing spatial and nonspatial working memory tasks.

The caudate nucleus is part of an anatomical network subserving functions associated with the dorsolateral prefrontal cortex (DLPFC). The aim of the present study was to investigate whether the metabolic activity in the striatum reflects specific changes in working memory tasks, which are known to be dependent on the DLPFC, and whether these changes reflect the topographic ordering of prefrontal connections within the striatum. Local cerebral glucose utilization (LCGU) rates were assessed in the striatum by the 14C-2-deoxyglucose method in monkeys that performed a spatial (delayed spatial alternation), a nonspatial (delayed object alternation) visual working memory task, or tasks that did not involve working memory, i.e., a visual pattern discrimination or sensorimotor paradigm. The results show a topographic segregation of activation related to spatial and nonspatial working memory, respectively. The delayed spatial alternation task increases LCGU rates bilaterally by 33-43% in the head of the caudate nucleus, where efferents from the dorsolateral prefrontal cortex project most densely. The delayed object alternation task enhances LCGU rates bilaterally by 32-37% in the body of the caudate nucleus, which is innervated by the temporal cortex. The visual pattern discrimination task similarly activated the body of the caudate, but in a smaller region and only in the right hemisphere. These findings provide the first evidence for metabolic activation of the caudate nuclei in working memory, supporting the role of this nucleus as a node in a neural network mediating DLPFC-dependent working memory processes. The double dissociation of activation observed suggests an anatomical and functional segregation of cortico-striatal circuits subserving spatial and nonspatial cognitive operations.

Animals↗
PubMed2003

Age-related working memory impairment is correlated with increases in the L-type calcium channel protein alpha1D (Cav1.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment.

The hippocampus is critical for spatial memory formation in rodents. Calcium currents through L-type voltage-sensitive calcium channels (L-VSCCs) are increased in CA1 neurons of the hippocampus of aged rats. We have recently shown that expression of the calcium conducting L-VSCC subunit alpha(1D) (Ca(v)1.3) is selectively increased in area CA1 of aged rats. We and others have speculated that excessive Ca(2+) influx through L-VSCC may be detrimental to memory formation. Therefore, we investigated the relationship between age-related working memory decline and alpha(1D) protein expression in the hippocampus. In addition, we studied the effects of chronic treatment with the L-VSCC antagonist nimodipine (NIM) on age-related working memory deficits and alpha(1D) expression in the hippocampus. Here we report that age-related increases in alpha(1D) expression in area CA1 correlate with working memory impairment in Fischer 344 rats. Furthermore, we demonstrate that chronic NIM treatment ameliorates age-related working memory deficits and reduces expression of alpha(1D) protein in the hippocampus. The present results suggest that L-VSCCs participate in processes underlying memory formation and that increases in L-VSCC protein and currents observed with aging may play a role in age-related memory decline. Furthermore, the amelioration in age-related memory decline produced by NIM treatment may be mediated, at least in part, by reductions in the abnormally high levels of alpha(1D) protein in the aged hippocampus. These findings may have implications for patients with Alzheimer's disease, who show increased L-VSCC protein expression in the hippocampus, and for patients receiving chronic treatment with L-VSCC antagonists.

Aging↗
PubMed1993

Coordinating information from perception and working memory.

Individuals must often coordinate information in working memory with information from perception. The demands of coordination have been analyzed in terms of the cost to switch attention. Coordination is considered in terms of the organization of control processes. Ss in 4 experiments performed list-processing tasks that sometimes required alternation between sets of items that were held in working memory or were currently displayed. Experiment 1 demonstrated that performance was slower and more error-prone when alternating between sets than when reporting a single set. On alternation tasks, latency varied with serial position, indicating that Ss paused between pairs of responses. In Experiment 2, this serial position function was observed for tasks requiring alternation between sets of information in the same modality (memory or perception). Experiments 3 and 4 demonstrate that this effect depends on the requirement to generate a new sequence of responses. A model of control processes for coordination is developed and tested.

Adult↗
PubMed2006

Working memory and information processing speed in children with myelomeningocele and shunted hydrocephalus: analysis of the children's paced auditory serial addition test.

Working memory and information processing speed were examined in children with myelomeningocele and shunted hydrocephalus using the Children's Paced Auditory Serial Addition Test (CHIPASAT). The CHIPASAT was administered to 31 children with myelomeningocele and shunted hydrocephalus and 27 healthy siblings, all between 8 and 15 years of age. They also completed other standardized measures of working memory and processing speed. Children with myelomeningocele made fewer correct responses than siblings, although the magnitude of group differences declined as the rate of stimulus presentation increased. Children with myelomeningocele also made fewer consecutive correct responses and were more likely to provide correct but nonconsecutive responses, suggesting that they responded in a way that circumvents the working memory demands of the task. Standardized measures of processing speed and working memory accounted for significant variance in CHIPASAT performance after controlling for age, group membership, math skill, and general intellectual functioning. The results indicate that children with myelomeningocele and shunted hydrocephalus display deficits in working memory and information processing speed, and suggest that the CHIPASAT may provide a valid measure of these skills.

Adolescent↗
PubMed1999

Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study.

OBJECTIVE: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI). BACKGROUND: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints. METHODS: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects. RESULTS: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups. CONCLUSION: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI.

Adult↗
PubMed2001

Awareness and working memory in strategy adaptivity.

To further the understanding of the mechanisms of strategy choice, in three experiments, we investigate the role of explicit awareness and working memory in strategy adaptivity. Experiment 1 provided correlational evidence that individual differences in strategy adaptivity to changing base rates are related to individual differences in awareness of those changes but appear not to be related to individual differences in working memory capacity. Experiment 2 replicated the role of awareness, and the results suggest that awareness at the time of the base-rate change, rather than afterwards, is related to increased strategy adaptivity. Experiment 3 measured working memory capacity using a different procedure and manipulated working memory load with a dual-task procedure; again, no apparent role of working memory capacity in strategy adaptivity was found. This juxtaposition of findings presents a challenge for existing models of strategy choice.

Adaptation, Psychological↗
PubMed2000

Integration of diverse information in working memory within the frontal lobe.

Ability to integrate diverse forms of information in current thought, or working memory, is essential for human reasoning and problem solving. We used functional imaging to identify brain regions preferentially involved in maintaining integrated versus unintegrated information in working memory. For equal amounts of verbal and spatial information, activation of prefrontal cortex was greater for maintaining integrated rather than unintegrated representations. Posterior brain regions showed the opposite pattern. These results demonstrate frontal-lobe specialization in maintaining working-memory representations that integrate verbal and spatial information. The role of prefrontal cortex in integrating multiple forms of information in working memory may underlie its unique contribution to high-level cognition that demands flexible mental representations.

Adult↗
PubMed2003

Spatiotemporal characteristics of dynamic feature binding in visual working memory.

It has been proposed that visual working memory can hold a set of four to five coherent object representations. As a test of this proposal, I devised a paradigm called multiple object permanence tracking (MOPT) that measures memory for feature-location binding in dynamic situations. Observers were asked to detect any feature switch in the middle of a regular rotation of a pattern with multiple objects behind an occluder. The feature switch detection performance dramatically declined as the pattern rotation velocity increased. The behavioral evidence for the use of multiple color-shape conjunction was observed only when the objects were stationary. These results cast doubt on the view that the functional unit of visual working memory involves coherent object representation, where object features are tightly bound and dynamically updated.

Color Perception↗
PubMed1995

Chronic administration of L-NAME in drinking water alters working memory in rats.

To examine the role of nitric oxide (NO) in the maintenance of working memory of rats, the effects of chronic administration (in drinking water) of the NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), on this behavior was examined with a simple test of remembering recently explored objects. Unlike other working memory tasks that require a subject to perform for a reward such as food or water or to avoid shock, our task measured spontaneous exploration of novel and familiar objects and has been described as a "pure" working memory task [9]. Normal subjects spend significantly more time in contact with new environmental components and less time with familiar objects. A subject that extensively reexplores a stimulus with which it has previous experience is presumed to exhibit some memory loss associated with the object. Memory changes were evaluated by measuring the relative time subjects explored familiar versus new stimulus objects. Rats (n = 15) that chronically drank L-NAME (approximately 90 mg/kg/day) for 14 days spent significantly less time exploring a novel object than did rats (n = 13) that drank only tap water (p < .05). This effect of L-NAME was abolished by concurrent administration of L-Arginine (approximately 4.5 g/kg/day). Total object exploration was not affected by our drug treatments, suggesting that our object discrimination task is not activity dependent. These data are consistent with the hypothesis that NO is required for some forms of working memory.

Analysis of Variance↗
PubMed2003

A recurrent network model of somatosensory parametric working memory in the prefrontal cortex.

A parametric working memory network stores the information of an analog stimulus in the form of persistent neural activity that is monotonically tuned to the stimulus. The family of persistent firing patterns with a continuous range of firing rates must all be realizable under exactly the same external conditions (during the delay when the transient stimulus is withdrawn). How this can be accomplished by neural mechanisms remains an unresolved question. Here we present a recurrent cortical network model of irregularly spiking neurons that was designed to simulate a somatosensory working memory experiment with behaving monkeys. Our model reproduces the observed positively and negatively monotonic persistent activity, and heterogeneous tuning curves of memory activity. We show that fine-tuning mathematically corresponds to a precise alignment of cusps in the bifurcation diagram of the network. Moreover, we show that the fine-tuned network can integrate stimulus inputs over several seconds. Assuming that such time integration occurs in neural populations downstream from a tonically persistent neural population, our model is able to account for the slow ramping-up and ramping-down behaviors of neurons observed in prefrontal cortex.

Action Potentials↗
PubMed1993

Working memory deficits following muscarinic blockade combined with depletion of brain somatostatin in rats.

In a working memory task with three-panel runway paradigm, cysteamine, a depletor of somatostatin, at 100 or 200 mg/kg i.p. given 24 h before testing, had no effect on the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). Cysteamine at 100 mg/kg caused a significant reduction in somatostatin-like immunoreactivity in the rat brain, including the hippocampus and cerebral cortex. Working memory errors were significantly increased by scopolamine, a muscarinic receptor antagonist, at 0.32 mg/kg i.p. given 20 min before testing, whereas errors were not affected by the 0.1 mg/kg dose. Combined administration of 100 mg/kg cysteamine and 0.1 mg/kg scopolamine significantly increased the number of working memory errors. However, cysteamine at 100 mg/kg and scopolamine at 0.1 mg/kg had no effect on reference memory errors, whether they were administered alone or in combination. These results suggest that depletion of brain somatostatin aggravates working memory deficits induced by blockade of muscarinic receptors.

Animals↗
PubMed2001

Primate rhinal cortex participates in both visual recognition and working memory tasks: functional mapping with 2-DG.

The rhinal cortex in the medial temporal lobe has been implicated in object recognition memory tasks and indeed is considered to be the critical node in a visual memory network. Previous studies using the 2-deoxyglucose method have shown that thalamic and hippocampal structures thought to be involved in visual recognition memory are also engaged by spatial and object working memory tasks in the nonhuman primate. Networks engaged in memory processing can be recognized by analysis of patterns of activation accompanying performance of specifically designed tasks. In the present study, we compared metabolic activation of the entorhinal and perirhinal cortex during the performance of three working memory tasks [delayed response (DR), delayed alternation (DA), and delayed object alternation (DOA)] to that induced by a standard recognition memory task [delayed match-to-sample (DMS)] and a sensorimotor control task in rhesus monkeys. A region-of-interest analysis revealed elevated local cerebral glucose utilization in the perirhinal cortex in animals performing the DA, DOA, and DMS tasks, and animals performing the DMS task were distinct in showing a strong focus of activation in the lateral perirhinal cortex. No significant differences were evident between groups performing memory and control tasks in the entorhinal cortex. These findings suggest that the perirhinal cortex may play a much broader role in memory processing than has been previously thought, encompassing explicit working memory as well as recognition memory.

Animals↗
PubMed2006

Dopamine modulation in the basal ganglia locks the gate to working memory.

The prefrontal cortex and basal ganglia are deeply implicated in working memory. Both structures are subject to dopaminergic neuromodulation in a way that exerts a critical influence on the proper operation of working memory. We present a novel network model to elucidate the role of phasic dopamine in the interaction of these two structures in initiating and maintaining mnemonic activity. We argue that neuromodulation plays a critical role in protecting memories against both internal and external sources of noise. Increases in cortical gain engendered by prefrontal dopamine release help make memories robust against external distraction, but do not offer protection against internal noise accompanying recurrent cortical activity. Rather, the output of the basal ganglia provides the gating function of stabilization against noise and distraction by enhancing select memories through targeted disinhibition of cortex. Dopamine in the basal ganglia effectively locks this gate by influencing the stability of up and down states in the striatum. Dopamine's involvement in affective processing endows this gating with specificity to motivational salience. We model a spatial working memory task and show that these combined effects of dopamine lead to superior performance.

Action Potentials↗
PubMed2002

[Role of the marginal division of human neostriatum in working memory capacity for numbers received through hearing: a functional magnetic resonance imaging study].

OBJECTIVE: With the help with functional magnetic resonance imaging (fMRI) technique, we aim to clarify whether the marginal division of the striatum (MrD) is involved in the working memory function of human brain for remembering numbers received through hearing. METHODS: Thirteen healthy volunteers were instructed to undertake both a working memory task, in which the subjects were asked to remember as many numbers read to them as possible, and a non-working memory control task, in which the subjects were not asked to remember the numbers. FMRI of the brain was performed in the 2 groups while the tests were being carried out separately, and the activity of the brain regions was compared between these 2 tasks. RESULTS: Eleven volunteers passed the working memory task for digit remembering. Highly active areas were observed in the prefrontal cortex and the MrD with predominance by the left side during performance of the working memory task, while other regions of the neostriatum were not excited. The prefrontal cortex and the MrD were not obviously activated during the performance in the control test. CONCLUSION: The results suggest that the MrD, along with the prefrontal cortex in the human brain, is involved in working memory function in remembering numbers assigned through hearing. The MrD is probably a subcortical memory center, which is linked to other memory-related brain areas.

Adult↗
PubMed2005

Visuo-verbal interactions in working memory: evidence from event-related potentials.

Working memory is thought to involve separate modality-specific storage systems. Interactions between these storage systems were investigated using a novel cross-modal 2-back paradigm. 2-back, 1-back and target items were presented either visually as a verbalizable linedrawing or auditorily as a digitized spoken word. ERPs for auditory targets were primarily modulated by the presentation modality of the 2-back item, whereas ERPs for visual targets were largely modulated by presentation modality of the 1-back item. Results indicate that verbalizable pictures are only partially transformed into a phonological code for rehearsal in working memory. Furthermore, results support the idea of a more stable and persistent auditory short-term store as opposed to a more transiently activated visual store for verbalizable material.

Acoustic Stimulation↗
PubMed2005

When high-powered people fail: working memory and "choking under pressure" in math.

We examined the relation between pressure-induced performance decrements, or "choking under pressure," in mathematical problem solving and individual differences in working memory capacity. In cognitively based academic skills such as math, pressure is thought to harm performance by reducing the working memory capacity available for skill execution. Results demonstrated that only individuals high in working memory capacity were harmed by performance pressure, and, furthermore, these skill decrements were limited to math problems with the highest demands on working memory capacity. These findings suggest that performance pressure harms individuals most qualified to succeed by consuming the working memory capacity that they rely on for their superior performance.

Adolescent↗